The major efforts of this project are aimed at understanding the molecular events in the life cycle of the human immunodeficiency viruses (HIV), especially type 1. Studies are currently focused on the following areas: 1) analyses of the viral regulatory genes, especially tat and rev, and how they act and are acted upon by host cellular factors; 2) studies of viral determinants which allow growth on specific cell types, such as macrophages; 3) correlation of proviral structure and integration with viral gene expression; 4) studies on how different genotypes of HIV-1 interact to confer new biological properties; 5) studies on viral ribonucleic acid expression from clinical materials and correlation with clinical states; 6) development of antisense oligonucleotides to inhibit various steps in the viral replication cycle; and 7) development of antiviral genes or nucleotide sequences and vectors for their delivery to the appropriate target cells.